title: Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Our recent studies of microRNA (miRNA) expression signatures demonstrated that microRNA-29s (miR-29s; miR-29a/b/c) were significantly downregulated in head and neck squamous cell carcinoma (HNSCC) and were putative tumour-suppressive miRNAs in human cancers. Our aim in this study was to investigate the functional significance of miR-29s in cancer cells and to identify novel miR-29s-mediated cancer pathways and responsible genes in HNSCC oncogenesis and metastasis.
  
  
  METHODS
  Gain-of-function studies using mature miR-29s were performed to investigate cell proliferation, migration and invasion in two HNSCC cell lines (SAS and FaDu). To identify miR-29s-mediated molecular pathways and targets, we utilised gene expression analysis and in silico database analysis. Loss-of-function assays were performed to investigate the functional significance of miR-29s target genes.
  
  
  RESULTS
  Restoration of miR-29s in SAS and FaDu cell lines revealed significant inhibition of cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that miR-29s modulated the focal adhesion pathway. Moreover, laminin γ2 (LAMC2) and α6 integrin (ITGA6) genes were candidate targets of the regulation of miR-29s. Luciferase reporter assays showed that miR-29s directly regulated LAMC2 and ITGA6. Silencing of LAMC2 and ITGA6 genes significantly inhibited cell migration and invasion in cancer cells.
  
  
  CONCLUSIONS
  Downregulation of miR-29s was a frequent event in HNSCC. The miR-29s acted as tumour suppressors and directly targeted laminin-integrin signalling. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and metastasis and suggests novel therapeutic strategies for the disease.
authors.affiliation: 1] Department of Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan [2] Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: N
authors.initials: N
authors.lastname: Nohata
authors.forename: T
authors.initials: T
authors.lastname: Hanazawa
authors.forename: N
authors.initials: N
authors.lastname: Kikkawa
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: T
authors.initials: T
authors.lastname: Itesako
authors.forename: H
authors.initials: H
authors.lastname: Enokida
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: N
authors.initials: N
authors.lastname: Seki
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000235:genetics*; D007797:Laminin / Q000235:genetics*; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016023:Integrins; D007797:Laminin; C532045:MIRN29a microRNA, human; D035683:MicroRNAs